Your disease

Biochemical overview

Propionic and methylmalonic acidaemias are caused by a deficiency of two enzymes involved in the catabolism of four amino acids: valine, isoleucine, methionine and threonine. These deficiencies manifest far down the metabolic pathway, which means it is not the precursor amino acids that accumulate, but derived substances: propionic acid and/or methylmalonic acid.

These substances are toxic to several organs (mainly the brain, but also the heart, kidneys, liver, etc.). Furthermore, these disorders lead to a secondary energy deficit.

  • These four-toxic precursor amino acids result from the breakdown of protein, whether exogenous (from food) or endogenous (from the breakdown of protein in body tissues).
  • Some bowel bacteria can also produce propionic acid (and, indirectly, methylmalonic acid).
  • More rarely, it can also come from the metabolism of certain fatty acids with an odd number of carbon atoms (which are rare in human foods). Treatment aims to limit the accumulation of toxic by-products while avoiding deficiencies and ensuring normal growth and development.

 


Diet

  • limited protein (and therefore, limited precursor amino acids), but with enough essential amino acids for growth (a mixture of essential amino acids without toxic precursor amino acids may be necessary),
  • enough energy to reduce catabolism (risk during intercurrent infections, fasting or anorexia, which is common in this group of children).

 

To achieve this, infants often need to be put on continuous enteral nutrition, at least at night.

  1. Treatment with L-carnitine, a medicine whose chemical properties allow it to bind with propionic acid and methylmalonic acid, followed by excretion in urine. This causes some extra clearance and helps to mitigate carnitine deficiency.
  2. Alternated antibiotic therapy, to modify the bowel flora and limit the production of propionic acid by bacteria in the bowel.
  3. Vitamin B12 supplementation helps certain patients with “B12-sensitive­” methylmalonic acidaemia to enhance residual enzyme activity and broaden the diet (increased tolerance).
  4. Vitamin H (biotin) supplementation is also used to treat some cases of propionic acidaemia.
Fig. 8: Diagram of treatment of propionic and methylmalonic acidaemias